Titel: PHIP-associated Chung-Jansen syndrome: report of 14 new individuals
ID: P-ClinG-068
Art: Postertalk
Redezeit: 2 min
Session: Poster Session
ClinG 2

Referent: Antje Kampmeier (Essen/DE), Alma Kuechler (Essen/DE)

Abstract - Text


In 2018, Jansen and colleagues described a new syndrome mainly characterized by developmental delay (DD), learning difficulties/intellectual disability (ID), behavioral abnormalities, facial dysmorphism and obesity due to haploinsufficiency of PHIP (pleckstrin homology domain interacting protein, OMIM *612870, CHUJANS, #617991). As currently less than 40 patients have been described, it still appears to be a rare cause of DD/ID.

In a collaborative effort, we collected 14 additional individuals with PHIP variants. While single base pair substitutions resulting in exchanges of specific amino acid residues or a premature stop of translation were identified by whole exomes sequencing, larger deletions affecting parts of PHIP or span the entire gene as well as adjacent genomic regions were detected by different types of array analyses. Confirmation testing (by Sanger sequencing, qPCR or FisH) and segregation analysis showed either de novo occurrence or inheritance from an also (mildly) affected parent. In accordance with previously described patients, all individuals reported here show developmental delay, learning disability or ID, behavioral abnormalities, weight problems with increasing age and characteristic craniofacial features (prominent eyebrows, thick alae nasi, and long philtrum).

Our findings further expand the mutational and clinical spectrum of PHIP. We discuss the molecular and clinical features in comparison to the published individuals. The fact that in some families the variant was inherited from a more mildly affected parent further illustrates the variability of the associated phenotype and underscores the importance of a thorough clinical evaluation.